Background/Aims: Superantigens are suspected of being potent initiators of gram-positive sepsis, and new therapies for superantigen elimination are required. The effects of hemoadsorption with a superantigen-adsorbing device (SAAD) were evaluated in septic swine. Methods: Toxic shock syndrome toxin-1 (TSST-1) was infused, and blood concentration was maintained at the clinical level for 6 h. Endotoxin was then infused to induce lethal shock. All animals were hemoperfused with SAAD or a control column for 8 h and changes in pathological parameters and mortality were examined. Results: Animals perfused with SAAD had a highly significant (p < 0.01) survival advantage compared with control groups at 24 h after initiation of the TSST-1 infusion. SAAD also suppressed the increase in the arteriovenous shunt ratio and decrease of partial arterial oxygen pressure at 6 h after TSST-1 infusion initiation. Conclusion: We suggest that there is a potential application of SAAD in treating superantigen-induced respiratory dysfunction and sepsis.